Azoline compounds
09968087 ยท 2018-05-15
Assignee
Inventors
Cpc classification
C07D409/12
CHEMISTRY; METALLURGY
C07D263/16
CHEMISTRY; METALLURGY
C07D261/04
CHEMISTRY; METALLURGY
A01N43/82
HUMAN NECESSITIES
C07D401/12
CHEMISTRY; METALLURGY
C07D207/22
CHEMISTRY; METALLURGY
C07D417/12
CHEMISTRY; METALLURGY
A61P43/00
HUMAN NECESSITIES
A01N43/80
HUMAN NECESSITIES
C07D413/12
CHEMISTRY; METALLURGY
C07D207/20
CHEMISTRY; METALLURGY
International classification
A01N43/80
HUMAN NECESSITIES
C07D207/22
CHEMISTRY; METALLURGY
A01N43/82
HUMAN NECESSITIES
C07D261/04
CHEMISTRY; METALLURGY
C07D401/12
CHEMISTRY; METALLURGY
C07D413/12
CHEMISTRY; METALLURGY
C07D417/12
CHEMISTRY; METALLURGY
C07D207/20
CHEMISTRY; METALLURGY
C07D409/12
CHEMISTRY; METALLURGY
C07D263/16
CHEMISTRY; METALLURGY
Abstract
The present invention relates to azoline compounds of formula I ##STR00001##
wherein A, B.sup.1, B.sup.2, B.sup.3, G.sup.1, G.sup.2, X.sup.1, R.sup.1, R.sup.3a, R.sup.3b, R.sup.g1 and R.sup.g2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
Claims
1. An azoline compound of the formula I ##STR00046## wherein X.sup.1 is O or CH.sub.2; A is a group of following formula: ##STR00047## wherein # denotes the bond to the aromatic ring of formula (I); W is selected from O and S; Y is selected from hydrogen, N(R.sup.5)R.sup.6 and OR.sup.9; B.sup.1, B.sup.2 and B.sup.3 are each independently CR.sup.2; G.sup.1 and G.sup.2 are each independently CR.sup.4; R.sup.g1 and R.sup.g2 form together a bridging group selected from CH.sub.2CH.sub.2CH.sub.2CH.sub.2 and CH.sub.2CH.sub.2CH.sub.2; R.sup.1 is CF.sub.3; each R.sup.2 is independently selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.2-haloalkoxy and C.sub.1-C.sub.2-haloalkyl; R.sup.3a, R.sup.3b are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, CO.sub.2R.sup.3d, C.sub.2-C.sub.3-alkenyl, C.sub.2-C.sub.3-alkynyl, C.sub.1-C.sub.3-alkoxy, C.sub.1-C.sub.3-haloalkoxy, C.sub.1-C.sub.3-haloalkylthio, C.sub.1-C.sub.3-alkylsulfonyl and C.sub.1-C.sub.3-haloalkylsulfonyl; or R.sup.3a and R.sup.3b together form a group O, C(R.sup.3c).sub.2, NOH or NOCH.sub.3; each R.sup.3c is independently selected from the group consisting of hydrogen, halogen, CH.sub.3 and CF.sub.3; R.sup.3d is selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.3-alkyloxy-C.sub.1-C.sub.3-alkyl-; each R.sup.4 is independently selected from the group consisting of hydrogen, halogen and cyano; R.sup.5 selected from hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.3-alkynyl and CH.sub.2CN; R.sup.6 is selected from hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-alkyl which carries one radical R.sup.8, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl which may be substituted by 1 or 2 substituents selected from F, CN and pyridyl;
N(R.sup.101a)R.sup.101b, wherein R.sup.101a is selected from hydrogen and C.sub.1-C.sub.6-alkyl; and R.sup.101b is selected from hydrogen, C(O)N(R.sup.14a)R.sup.14b, wherein R.sup.14a is selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl; and R.sup.14b is selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.4-alkynyl, CH.sub.2CN, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; phenyl, optionally substituted with 1, 2, 3, 4 or 5 substituents R.sup.16, and a heterocyclic ring selected from rings of formulae E-1 to E-42 ##STR00048## ##STR00049## ##STR00050## ##STR00051## ##STR00052## where in these rings E-1 to E-42 as a meaning for R.sup.101b the zigzag line denotes the attachment point to the remainder of the molecule; k is 0, 1, 2 or 3, and each R.sup.16 is independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylsulfinyl, C.sub.1-C.sub.4-haloalkylsulfinyl, C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, aminocarbonyl, C.sub.1-C.sub.4-alkylaminocarbonyl and di-(C.sub.1-C.sub.4-alkyl)aminocarbonyl; CHNOR.sup.9a, wherein R.sup.9a is selected from hydrogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-haloalkyl; phenyl which may be substituted with 1, 2, 3, 4, or 5 substituents R.sup.11, and a 3-, 4-, 5- or 6-membered saturated, partially unsaturated or maximally unsaturated heteromonocyclic ring containing 1, 2 or 3 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO and SO.sub.2, as ring members, where the heteromonocyclic ring may be substituted with one or more substituents R.sup.11; wherein each R.sup.11 is independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl and C.sub.2-C.sub.4-haloalkynyl; or two R.sup.11 present on the same carbon atom of a saturated heterocyclic ring may form together O or S; or two R.sup.11 present on the same S or SO ring member of a heterocyclic ring may together form a group N(C.sub.1-C.sub.6-alkyl), NO(C.sub.1-C.sub.6-alkyl), NN(H)(C.sub.1-C.sub.6-alkyl) or NN(C.sub.1-C.sub.6-alkyl).sub.2; each R.sup.8 is independently selected from OH, CN, C.sub.3-C.sub.8-cycloalkyl which optionally carries a CN or a C.sub.1-C.sub.2-haloalkyl substituent; C.sub.3-C.sub.8-halocycloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.1-C.sub.6-haloalkylsulfonyl, C(O)N(R.sup.102a)R.sup.102b, phenyl, optionally substituted with 1, 2, 3, 4 or 5 substituents R.sup.16, and a 3-, 4-, 5- or 6-membered saturated, partially unsaturated or maximally unsaturated heteromonocyclic ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO and SO.sub.2, as ring members, where the heteromonocyclic ring may be substituted with one or more substituents R.sup.16; wherein R.sup.102a is selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.3-alkynyl and CH.sub.2CN; R.sup.102b is selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, CH.sub.2CN, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.3-C.sub.6-cycloalkylmethyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio and C.sub.1-C.sub.4-haloalkylthio; and a heterocyclic ring selected from rings of formulae E-1 to E-42 as defined above and E-43 to E-57: ##STR00053## ##STR00054## where in these rings E-43 to E-57 the zigzag line denotes the attachment point to the remainder of the molecule; k is 0, 1, 2 or 3, n is 0, 1 or 2; and each R.sup.16 is independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylsulfinyl, C.sub.1-C.sub.4-haloalkylsulfinyl, C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, aminocarbonyl, C.sub.1-C.sub.4-alkylaminocarbonyl and di-(C.sub.1-C.sub.4-alkyl)aminocarbonyl; or two R.sup.16 present on the same carbon atom of a saturated ring may form together O or S; and each R.sup.16 as a substituent on phenyl (as a meaning of R.sup.8) or the heterocyclic rings (as a meaning of R.sup.8) is independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl and C.sub.2-C.sub.4-haloalkynyl; or two R.sup.16 present on the same carbon atom of a saturated heterocyclic ring may form together O or S; or two R.sup.16 present on the same S or SO ring member of a heterocyclic ring may together form a group N(C.sub.1-C.sub.6-alkyl), NO(C.sub.1-C.sub.6-alkyl), NN(H)(C.sub.1-C.sub.6-alkyl) or NN(C.sub.1-C.sub.6-alkyl).sub.2; or R.sup.5 and R.sup.6, together with the nitrogen atom to which they are bound, form a 5- or 6-membered saturated heterocyclic ring, where the ring may further contain 1 or 2 heteroatoms or heteroatom-containing groups selected from O, S, SO, SO.sub.2, NH and CO as ring members, wherein the heterocyclic ring may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy and C.sub.1-C.sub.6-haloalkoxy; or R.sup.5 and R.sup.6 together form a group S(R.sup.9b).sub.2, where R.sup.9b is selected from C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-haloalkyl; R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl and C.sub.1-C.sub.6-alkyl substituted by one radical R.sup.13; where R.sup.13 is selected from CN, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.1-C.sub.6-alkylsulfinyl, C.sub.1-C.sub.6-haloalkylsulfinyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.1-C.sub.6-haloalkylsulfonyl and a heterocyclic ring selected from rings of formulae E-1 to E-57 as defined above; where in these rings E-1 to E-57 as a meaning of R.sup.13 the zigzag line denotes the attachment point to the remainder of the molecule; k is 0, 1, 2 or 3, n is 0, 1 or 2; and each R.sup.16 is independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylsulfinyl, C.sub.1-C.sub.4-haloalkylsulfinyl, C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, aminocarbonyl, C.sub.1-C.sub.4-alkylaminocarbonyl and di-(C.sub.1-C.sub.4-alkyl)amino-carbonyl; or two R.sup.16 present on the same carbon atom of a saturated ring may form together O or S; and each R.sup.16 in all other cases is independently selected from the group consisting of halogen, nitro, cyano, OH, SH, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.1-C.sub.6-alkylsulfinyl, C.sub.1-C.sub.6-haloalkylsulfinyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.1-C.sub.6-haloalkylsulfonyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-haloalkoxycarbonyl, aminocarbonyl, C.sub.1-C.sub.4-alkylaminocarbonyl, di-(C.sub.1-C.sub.4-alkyl)-aminocarbonyl, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl; C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, wherein the three last-mentioned aliphatic radicals may be unsubstituted, partially or fully halogenated and/or may carry 1 or 2 radicals selected from cyano, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy and oxo; C.sub.3-C.sub.8-cycloalkyl which may be unsubstituted, partially or fully halogenated and/or may carry 1 or 2 radicals selected from cyano, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy and oxo; phenyl, benzyl, pyridyl and phenoxy, wherein the four last mentioned radicals may be unsubstituted, partially or fully halogenated and/or carry 1, 2 or 3 substituents selected from C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy and (C.sub.1-C.sub.6-alkoxy)carbonyl; or two R.sup.16 present together on the same atom of an unsaturated or partially unsaturated ring may be O, S, N(C.sub.1-C.sub.6-alkyl), NO(C.sub.1-C.sub.6-alkyl), CH(C.sub.1-C.sub.4-alkyl) or C(C.sub.1-C.sub.4-alkyl)C.sub.1-C.sub.4-alkyl; or or two R.sup.16 present on the same S or SO ring member of a heterocyclic ring may together form a group N(C.sub.1-C.sub.6-alkyl), NO(C.sub.1-C.sub.6-alkyl), NN(H)(C.sub.1-C.sub.6-alkyl) or NN(C.sub.1-C.sub.6-alkyl).sub.2; or two R.sup.16 on two adjacent carbon atoms form together with the carbon atoms they are bonded to a 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring, wherein the ring may contain 1 or 2 heteroatoms or heteroatom groups selected from N, O, S, NO, SO and SO.sub.2, as ring members, and wherein the ring optionally carries one or more substituents selected from halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; and the N-oxides, stereoisomers and agriculturally or veterinarily acceptable salts thereof.
2. The compound as claimed in claim 1, where each R.sup.8 is independently selected from OH, CN, C.sub.3-C.sub.8-cycloalkyl which optionally carries a CN or CF.sub.3 substituent, C.sub.3-C.sub.8-halocycloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.1-C.sub.6-haloalkylsulfonyl, C(O)N(R.sup.102a)R.sup.102b, phenyl, optionally substituted with 1, 2, 3, 4 or 5 substituents R.sup.16, and a 3-, 4-, 5- or 6-membered saturated, partially unsaturated or maximally unsaturated heteromonocyclic ring containing 1, 2 or 3 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO and SO.sub.2, as ring members, where the heteromonocyclic ring may be substituted with one or more substituents R.sup.16; where R.sup.102a, R.sup.102b and R.sup.16 are as defined in claim 1.
3. The compound as claimed in claim 1, where X.sup.1 is O.
4. The compound as claimed in claim 1, where X.sup.1 is CH.sub.2.
5. The compound as claimed in claim 1, where W is O.
6. The compound as claimed in claim 1, where in A Y is OR.sup.9.
7. The compound as claimed in claim 1, where in A Y is N(R.sup.5)R.sup.6; wherein R.sup.5 and R.sup.6 are as defined in claim 1.
8. The compound as claimed in claim 7, where R.sup.5 is hydrogen or C.sub.1-C.sub.3-alkyl; R.sup.6 is selected from hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.4-alkyl which carries one radical R.sup.8, wherein R.sup.8 is as defined below; C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl which may be substituted by 1 or 2 substituents selected from F, CN and pyridyl;
N(R.sup.101a)R.sup.101b, wherein R.sup.101a is selected from hydrogen and C.sub.1-C.sub.6-alkyl; and R.sup.101b is selected from hydrogen, C(O)N(R.sup.14a)R.sup.14b, wherein R.sup.14a is selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl; and R.sup.14b is selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.4-alkynyl, CH.sub.2CN, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; phenyl, optionally substituted with 1, 2, 3, 4 or 5 substituents wherein R.sup.16 is as defined below; and a heteroaromatic ring selected from rings of formulae E-1 to E-42 as defined in claim 1; CHNOR.sup.9a, wherein R.sup.9a is selected from hydrogen, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-haloalkyl; phenyl which may be substituted with 1, 2, 3, 4, or 5 substituents R.sup.11, wherein R.sup.11 is as defined below; and a heteromonocyclic ring selected from rings of formulae F-1 to F-60 ##STR00055## ##STR00056## ##STR00057## ##STR00058## ##STR00059## ##STR00060## ##STR00061## wherein the zigzag line denotes the attachment point to the remainder of the molecule; k is 0, 1, 2 or 3, n is 0, 1 or 2, and each R.sup.11 is independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylsulfinyl, C.sub.1-C.sub.4-haloalkylsulfinyl, C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, aminocarbonyl, C.sub.1-C.sub.4-alkylaminocarbonyl and di-(C.sub.1-C.sub.4-alkyl)-aminocarbonyl; or two R.sup.11 present on the same carbon atom of a saturated or partially unsaturated heterocyclic ring may form together O or S; or two R.sup.11 present on the same S or SO ring member of a heterocyclic ring may together form a group N(C.sub.1-C.sub.6-alkyl), NO(C.sub.1-C.sub.6-alkyl), NN(H)(C.sub.1-C.sub.6-alkyl) or NN(C.sub.1-C.sub.6-alkyl).sub.2; R.sup.8 is selected from OH, CN, C.sub.3-C.sub.8-cycloalkyl which optionally carries a CN, CHF.sub.2 or CF.sub.3 substituent, C.sub.3-C.sub.8-halocycloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.1-C.sub.6-alkylsulfinyl, C.sub.1-C.sub.6-haloalkylsulfinyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.1-C.sub.6-haloalkylsulfonyl, C(O)N(R.sup.102a)R.sup.102b, phenyl, optionally substituted with 1, 2, 3, 4 or 5 substituents R.sup.16, and a heterocyclic ring selected from rings of formulae E-1 to E-57 as defined in claim 1 and additionally from 1,3-dioxolan-2-yl which may carry 1, 2 or 3 substituents R.sup.16 as defined in claim 1; wherein R.sup.102a is selected from the group consisting of hydrogen and C.sub.1-C.sub.6-alkyl; R.sup.102b is selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.4-alkynyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, CH.sub.2CN, C.sub.1-C.sub.6-alkoxy and C.sub.1-C.sub.6-haloalkoxy; and each R.sup.16 as a substituent on phenyl or heterocyclic rings of formulae E-1 to E-57 is independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylsulfinyl, C.sub.1-C.sub.4-haloalkylsulfinyl, C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, aminocarbonyl, C.sub.1-C.sub.4-alkylaminocarbonyl and di-(C.sub.1-C.sub.4-alkyl)-aminocarbonyl; or two R.sup.16 present on the same carbon atom of a saturated heterocyclic ring may form together O or S; or two R.sup.16 present on the same S or SO ring member of a heterocyclic ring may together form a group N(C.sub.1-C.sub.6-alkyl), NO(C.sub.1-C.sub.6-alkyl), NN(H)(C.sub.1-C.sub.6-alkyl) or NN(C.sub.1-C.sub.6-alkyl).sub.2.
9. The compound as claimed in claim 8, where R.sup.5 is as defined in claim 8; R.sup.6 is selected from hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.4-alkyl which carries one radical R.sup.8, wherein R.sup.8 is as defined below; C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl which may be substituted by 1 or 2 substituents selected from F, CN and pyridyl; N(R.sup.101a)R.sup.101b, wherein R.sup.101a and R.sup.101b are as defined in claim 8; CHNOR.sup.9a, wherein R.sup.9a is as defined in claim 8; phenyl which may be substituted with 1, 2, 3, 4, or 5 substituents R.sup.11, wherein R.sup.11 is as defined below; and a heteromonocyclic ring selected from rings of formulae F-1 to F-57 as defined in claim 8; wherein R.sup.8 is selected from OH, CN, C.sub.3-C.sub.8-cycloalkyl which optionally carries a CN or CF.sub.3 substituent, C.sub.3-C.sub.8-halocycloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.1-C.sub.6-alkylsulfinyl, C.sub.1-C.sub.6-haloalkylsulfinyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.1-C.sub.6-haloalkylsulfonyl, C(O)N(R.sup.102a)R.sup.102b, phenyl, optionally substituted with 1, 2, 3, 4 or 5 substituents R.sup.16, and a heterocyclic ring selected from rings of formulae E-1 to E-57 as defined in claim 1; wherein R.sup.102a, R.sup.102b, and R.sup.16 are as defined in claim 8; and each R.sup.11 is independently selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio, C.sub.1-C.sub.4-haloalkylthio, C.sub.1-C.sub.4-alkylsulfinyl, C.sub.1-C.sub.4-haloalkylsulfinyl, C.sub.1-C.sub.4-alkylsulfonyl, C.sub.1-C.sub.4-haloalkylsulfonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, aminocarbonyl, C.sub.1-C.sub.4-alkylaminocarbonyl and di-(C.sub.1-C.sub.4-alkyl)-aminocarbonyl; or two R.sup.11 present on the same carbon atom of a saturated heterocyclic ring may form together O or S; or two R.sup.11 present on the same S or SO ring member of a heterocyclic ring may together form a group N(C.sub.1-C.sub.6-alkyl), NO(C.sub.1-C.sub.6-alkyl), NN(H)(C.sub.1-C.sub.6-alkyl) or NN(C.sub.1-C.sub.6-alkyl).sub.2.
10. The compound as claimed in claim 1, where the saturated heteromonocyclic ring R.sup.6 is selected from rings of formulae F-44-1 and F-53-1, and the heterocyclic ring R.sup.8 is selected from rings of formulae E-44-1 and E-57-1 ##STR00062## wherein n is 0, 1 or 2; and R.sup.17 is selected from the group consisting of hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.2-C.sub.4-haloalkynyl and CH.sub.2(C.sub.3-C.sub.6-cycloalkyl).
11. The compound as claimed in claim 1, where B.sup.1 is CR.sup.2, where R.sup.2 is not hydrogen, and B.sup.2 and B.sup.3 are CR.sup.2, where R.sup.2 is selected from hydrogen, F, Cl, Br, OCF.sub.3 and CF.sub.3.
12. The compounds as claimed in claim 1, where R.sup.4 is hydrogen.
13. The compound as claimed in claim 1, where R.sup.g1 and R.sup.g2 form together a bridging group CH.sub.2CH.sub.2CH.sub.2.
14. The compound as claimed in claim 1, where R.sup.g1 and R.sup.g2 form together a bridging group CH.sub.2CH.sub.2CH.sub.2CH.sub.2.
15. The compound as claimed in claim 1, where R.sup.3a and R.sup.3b are hydrogen or fluorine.
16. The compound as claimed in claim 1, of formula IB ##STR00063## wherein R.sup.2a is Cl, R.sup.2b is F, R.sup.2c is Cl, and R.sup.6 is CH.sub.2C(O)N(H)R.sup.102b, wherein R.sup.102b is selected from the group consisting of C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkyl substituted with 1 or 2 fluorine atoms, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, CH.sub.2CN, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl and C.sub.3-C.sub.6-cycloalkylmethyl; and the stereoisomers and agriculturally or veterinarily acceptable salts thereof.
17. The compound as claimed in claim 1, of formula IB as defined in claim 16, wherein R.sup.2a is Cl, R.sup.2b is F, R.sup.2c is Cl, and R.sup.6 is CH.sub.2R.sup.8, wherein R.sup.8 is selected from rings E-5, E-6, E-7, E-19, E-25, E-27, E-44-1 and E-57-1 as defined in claim 1, where the rings E-5, E-6, E-7, E-19 and E-27 are unsubstituted (k is 0) or carry 1 or 2 substituents R.sup.16 (k is 1 or 2), wherein each R.sup.16 is independently selected from halogen, cyano, nitro, C.sub.1-C.sub.2-alkyl, C.sub.1-C.sub.2-haloalkyl, C.sub.1-C.sub.2-alkoxy, C.sub.1-C.sub.2-haloalkoxy, C.sub.1-C.sub.2-alkylthio, C.sub.1-C.sub.2-haloalkylthio, C.sub.1-C.sub.2-alkylsulfinyl, C.sub.1-C.sub.2-haloalkylsulfinyl, C.sub.1-C.sub.2-alkylsulfonyl, C.sub.1-C.sub.2-haloalkylsulfonyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.3-C.sub.4-halocycloalkyl, C.sub.2-C.sub.3-alkenyl, C.sub.2-C.sub.3-alkynyl; and where ring E-25 carries one substituent R.sup.16 on the nitrogen atom in the 1-position and optionally carries 1 or 2 further substituents R.sup.16, where R.sup.16 is as defined above; where however R.sup.16 bound in the 1-position is not is not halogen, cyano, nitro, C.sub.1-C.sub.2-alkoxy, C.sub.1-C.sub.2-haloalkoxy, C.sub.1-C.sub.2-alkylthio, C.sub.1-C.sub.2-haloalkylthio, C.sub.1-C.sub.2-alkylsulfinyl, C.sub.1-C.sub.2-haloalkylsulfinyl, C.sub.1-C.sub.2-alkylsulfonyl or C.sub.1-C.sub.2-haloalkylsulfonyl; and the stereoisomers and agriculturally or veterinarily acceptable salts thereof.
18. The compound as claimed in claim 1, of formula IB as defined in claim 16, wherein R.sup.2a is Cl, R.sup.2b is F, R.sup.2c is Cl, and R.sup.6 is selected from rings F-2, F-4, F-6, F-8, F-9, F-44-1, F-46, F-51 and F-53-1 as defined in claim 8, where the rings F-2, F-4, F-6, F-8, F-9 and F-46 are unsubstituted (k is 0) or carry 1 or 2 substituents R.sup.11 (k is 1 or 2), wherein each R.sup.11 is independently selected from halogen, cyano, nitro, C.sub.1-C.sub.2-alkyl, C.sub.1-C.sub.2-alkoxy, C.sub.1-C.sub.2-haloalkoxy, C.sub.1-C.sub.2-haloalkylthio, C.sub.1-C.sub.2-alkylsulfonyl, C.sub.1-C.sub.2-haloalkylsulfonyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.3-C.sub.4-halocycloalkyl, C.sub.2-C.sub.3-alkenyl and C.sub.2-C.sub.3-alkynyl; and where ring F-51 is a ring of formula F-51-1 ##STR00064## wherein R.sup.18 is selected from the group consisting of hydrogen, C.sub.1-C.sub.2-alkyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.3-C.sub.4-halocycloalkyl, C.sub.2-C.sub.3-alkenyl and C.sub.2-C.sub.3-alkynyl; and the stereoisomers and agriculturally or veterinarily acceptable salts thereof.
19. The compound as claimed in claim 1, of formula IB as defined in claim 16, wherein R.sup.2a is Cl, R.sup.2b is F, R.sup.2c is Cl, and R.sup.6 is selected from C.sub.2-C.sub.4-alkyl which may be substituted with 1 or 2 fluorine atoms, cyclopropyl, C.sub.3-C.sub.5-halocycloalkyl, CH.sub.2(C.sub.3-C.sub.5-halocycloalkyl), CH.sub.2-(1-cyano-(C.sub.3-C.sub.5-cycloalkyl)), C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, CH.sub.2CN and CHNOR.sup.9a, wherein R.sup.9a is selected from C.sub.1-C.sub.3-alkyl and C.sub.1-C.sub.3-haloalkyl; and the stereoisomers and agriculturally or veterinarily acceptable salts thereof.
20. The compound as claimed in claim 1, of formula IB as defined in claim 16, wherein R.sup.2a is Cl, R.sup.2b is F, R.sup.2c is Cl, and R.sup.6 is N(H)R.sup.101b, wherein R.sup.101b is selected from C(O)N(H)R.sup.14b and rings E-1 and E-7 as defined in claim 1, where R.sup.14b is selected from C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-haloalkyl and cyclopropyl; and where in rings E-1 and E-7 k is 0, 1 or 2; and each R.sup.16 is independently selected from halogen, cyano, nitro, C.sub.1-C.sub.2-alkyl, C.sub.1-C.sub.2-haloalkyl, C.sub.1-C.sub.2-alkoxy, C.sub.1-C.sub.2-haloalkoxy, C.sub.1-C.sub.2-alkylthio, C.sub.1-C.sub.2-haloalkylthio, C.sub.1-C.sub.2-alkylsulfinyl, C.sub.1-C.sub.2-haloalkylsulfinyl, C.sub.1-C.sub.2-alkylsulfonyl, C.sub.1-C.sub.2-haloalkylsulfonyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.3-C.sub.4-halocycloalkyl, C.sub.2-C.sub.3-alkenyl, C.sub.2-C.sub.3-alkynyl; and the stereoisomers and agriculturally or veterinarily acceptable salts thereof.
21. An agricultural or veterinary composition comprising at least one compound of the formula I, as defined in claim 1, a stereoisomer thereof and/or at least one agriculturally or veterinarily acceptable salt thereof, and at least one inert liquid and/or solid agriculturally or veterinarily acceptable carrier.
22. A method for controlling invertebrate pests which method comprises treating the pests, their food supply, their habitat or their breeding ground or a cultivated plant, plant propagation materials, soil, area, material or environment in which the pests are growing or may grow, or the materials, cultivated plants, plant propagation materials, soils, surfaces or spaces to be protected from pest attack or infestation with a pesticidally effective amount of a compound of claim 1 or stereoisomer and/or an agriculturally acceptable salt thereof.
23. A method for protecting plant propagation material and/or the plants which grow therefrom from attack or infestation by invertebrate pests, which method comprises treating the plant propagation material with a pesticidally effective amount of at least one compound of the formula I as defined in claim 1, a stereoisomer and/or at least one agriculturally acceptable salt thereof.
Description
EXAMPLES
(1) The present invention is now illustrated in further details by the following examples, without imposing any limitation thereto.
I. Preparation Examples
(2) Compounds can be characterized e.g. by coupled High Performance Liquid Chromatography/mass spectrometry (HPLC/MS), by .sup.1H-NMR and/or by their melting points.
(3) Analytical HPLC Column:
(4) Method A: Analytical UPLC column: Phenomenex Kinetex 1.7 m XB-C18 100A; 502.1 mm from Phenomenex, Germany. Elution: acetonitrile+0.1% trifluoroacetic acid (TFA)/water+0.1% trifluoroacetic acid (TFA) in a ratio from 5:95 to 100:0 in 1.5 min at 60 C. Flow: 0.8 mL/min to 1 mL/min in 1.5 min. MS-method: ESI positive.
(5) .sup.1H-NMR: The signals are characterized by chemical shift (ppm, [delta]) vs. tetramethylsilane, respectively CDCl.sub.3 for .sup.13C-NMR, by their multiplicity and by their integral (relative number of hydrogen atoms given). The following abbreviations are used to characterize the multiplicity of the signals: m=multiplet, q=quartet, t=triplet, d=doublet and s=singlet.
(6) Abbreviations used are: d for day(s), h for hour(s), min for minute(s), r.t./room temperature for 20-25 C., THF for tetrahydrofuran, DCE for dichloroethane, PyBroP for bromotripyrrolidinophosphonium hexafluorophosphate.
C.1 Compound Examples 1
(7) Compound examples 1-1 to 1-138 correspond to compounds of formula C.1:
(8) ##STR00040##
wherein R.sup.2a, R.sup.2b, R.sup.2c and Y of each synthesized compound is defined in one row of table C.1 below.
(9) The compounds were synthesized in analogy to Synthesis Example S.1.
(10) TABLE-US-00002 TABLE C.1 HPLC-MS: Method, R.sub.t (min) & [M + H].sup.+ or Ex. R.sup.2a, R.sup.2b, R.sup.2c Y .sup.1H-NMR 1-1 Cl, F, Cl OCH.sub.3 A 1.559 477.5 1-2 Cl, F, Cl OH A 1.446 461.4 1-3 Cl, F, Cl NHCH.sub.2-cyclopropyl .sup.1H NMR (400 MHz, CDCl.sub.3): 7.6 (m, 2H), 7.5 (m, 1H), 7.2 (m, 1H), 6.0 (s, 1H), 4.2 (d, 1H), 3.8 (d, 1H), 3.4-3.3 (m, 2H), 3.3-3.1 (m, 4H), 2.2-2.1 (m, 2H), 1.1-1.0 (m, 1H), 0.6-0.5 (m, 2H), 0.3-0.2 (m, 2H). 1-4 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.2CF.sub.3 A 1.355 599.8 1-5 Cl, F, Cl NH-(1,1-dioxo-thietan-3-yl) A 1.402 564.3 1-6 Cl, F, Cl NHCH.sub.2-(2-pyridyl) A 1.248 551.4 1-7 Cl, F, Cl NHCH.sub.2-(2-pyrimidinyl) A 1.432 552.4 1-8 Cl, F, Cl NHCH.sub.2-(thietan-3-yl) A 1.464 546.8 1-9 Cl, F, Cl NH-(thietan-3-yl) A 1.460 532.8 1-10 Cl, F, Cl NH-(1-oxo-thietan-3-yl) A 1.305 548.8 1-11 Cl, F, Cl NHCH.sub.2CHCH.sub.2 A 1.440 500.8 1-12 Cl, F, Cl NHCH.sub.2CF.sub.3 A 1.467 542.8 1-13 Cl, F, Cl NH-(1-cyano-cyclopropyl) A 1.410 525.9 1-14 Cl, F, Cl NHCH.sub.2CCH A 1.409 498.8 1-15 Cl, F, Cl NH.sub.2 A 1.460 460.4 1-16 Cl, F, Cl NHNH-(2-pyrimidinyl) A 1.446 553.4 1-17 Cl, F, Cl NHCH.sub.2CN A 1.515 499.4 1-18 Cl, F, Cl NHCH.sub.2-(1,1-dioxo-thietan-3-yl) A 1.342 578.9 1-19 Cl, F, Cl NH-(2,2-dimethyl-1,1-dioxo- A 1.430 592.9 thietan-3-yl) 1-20 Cl, F, Cl NH-(2,2-dimethylthietan-3-yl) A 1.538 561.3 1-21 Cl, F, Cl NHCH.sub.2-(1,1-dioxothietan-2-yl) A 1.372 579.3 1-22 Cl, F, Cl NHCH.sub.2CHCHCH.sub.3 (trans) A 1.479 514.9 1-23 Cl, F, Cl NHCHNOCH.sub.3 A 1.513 518.0 1-24 Cl, H, Cl NH.sub.2 A 1.319 442.9 1-25 Cl, H, Cl NHNH-(2-pyrimidinyl) A 1.317 535.9 1-26 Cl, H, Cl NHCHNOCH.sub.3 A 1.488 500.0 1-27 Cl, H, Cl NHCH.sub.2-(2-pyridyl) A 1.259 534.0 1-28 Cl, H, Cl NHCH.sub.2C(O)NHCH.sub.2CF.sub.3 A 1.369 582.0 1-29 Cl, H, Cl NHCH.sub.2CF.sub.3 A 1.463 524.9 1-30 Cl, H, Cl NHCH.sub.2-(2-pyrimidinyl) A 1.357 535.0 1-31 Cl, H, Cl NH-cyclopropyl A 1.404 483.0 1-32 Cl, H, Cl NHCH.sub.2-(thiazol-4-yl) A 1.380 539.9 1-33 Cl, H, Cl NH-(1,1-dioxo-thietan-3-yl) A 1.347 547.0 1-34 Cl, H, Cl NH-(thietan-3-yl) A 1.450 514.9 1-35 Cl, H, Cl NHCH.sub.2-cyclopropyl A 1.456 496.9 1-36 Cl, H, Cl NHCH.sub.2-(1,1-dioxo-thietan-3-yl) A 1.353 561.0 1-37 Cl, H, Cl NHCH(CH.sub.3)C(O)NHCH.sub.2CF.sub.3 A 1.403 596.0 1-38 Cl, H, Cl NH-[(4R)-2-ethyl-3-oxo- A 1.377 556.0 isoxazolidin-4-yl] 1-39 Cl, H, Cl NH-[(4R)-3-oxo-2-(2,2,2- A 1.425 609.9 trifluoroethyl)isoxazolidin-4-yl] 1-40 Cl, H, Cl N(CH.sub.3)CH.sub.2-(2-pyridyl) A 1.284 548.5 1-41 Cl, H, Cl N(CH.sub.2CH.sub.3)CH.sub.2-(2-pyridyl) A 1.313 562.1 1-42 Cl, H, Cl NH-(1-oxo-thietan-3-yl) A 1.304 531.0 1-43 Cl, H, Cl NH-[(4S)-2-ethyl-3-oxo- A 1.396 556.0 isoxazolidin-4-yl] 1-44 Cl, F, Cl NHCH.sub.2CH.sub.3 A 1.428 489.0 1-45 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.2CH.sub.3 A 1.350 548.0 1-46 Cl, F, Cl NH-cyclopropyl A 1.430 503.0 1-47 Cl, F, Cl NHCH.sub.2C(O)NH-cyclopropyl A 1.358 558.0 1-48 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.2CH.sub.2F A 1.334 564.0 1-49 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.2CHF.sub.2 A 1.359 582.0 1-50 Cl, F, Cl NHCH.sub.2-(2,2- A 1.466 551.0 difluorocyclopropyl) 1-51 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.2CCH A 1.347 556.0 1-52 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.2CHCH.sub.2 A 1.368 558.0 1-53 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.3 A 1.315 532.0 1-54 Cl, F, Cl NHCH.sub.2-(4-thiazolyl) A 1.402 558.0 1-55 Cl, F, Cl NH-(3-tetrahydrofuranyl) A 1.395 531.0 1-56 Cl, H, Cl OH .sup.1H NMR (400 MHz, CDCl.sub.3): 7.96 (d, 1H), 7.51 (s, 2H), 7.43 (s, 1H), 7.26 (d, 1H), 4.15 (d, 1H), 3.76 (d, 1H), 3.40-3.33 (m, 2H), 3.24-3.20 (m, 2H), 2.20-2.10 (m, 2H) 1-57 Cl, H, Cl NHCH.sub.2-(thietan-3-yl) A 1.446 529.0 1-58 Cl, F, Cl NHCH.sub.2-cyclobutyl A 1.524 529.1 1-59 Cl, F, Cl NH-(3,3-difluorocyclobutyl) A 1.471 551.0 1-60 Cl, F, Cl NHCH.sub.2-(3,3- A 1.477 565.0 difluorocyclobutyl) 1-61 Cl, F, Cl NH-[(4R)-3-oxo-2-(2,2,2- A 1.426 627.9 trifluoroethyl)isoxazolidin-4-yl] 1-62 Cl, F, Cl NH-[(4S)-2-ethyl-3-oxo- A 1.385 574.0 isoxazolidin-4-yl] 1-63 Cl, F, Cl NHCH.sub.2-(3-pyridazinyl) A 1.303 552.9 1-64 Cl, F, Cl NHCH.sub.2-(5-bromopyrimidin-2-yl) A 1.454 632.8 1-65 Cl, F, Cl NHCH.sub.2-[(1-difluoromethyl)cyclopropyl] A 1.464 564.9 1-66 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.2- A 1.394 572.0 cyclopropyl 1-67 Cl, F, Cl NH-cyclobutyl A 1.466 514.9 1-68 Cl, F, Cl NHCH.sub.2-[4,6-bis(trifluoro- A 1.546 689.0 methyl)pyrimidin-2-yl] 1-69 Cl, F, Cl NHCH.sub.2-(2,2- A 1.526 584.9 dichlorocyclopropyl) 1-70 Cl, F, Cl NHCH.sub.2CClCCl.sub.2 A 1.560 604.9 1-71 Cl, F, Cl NHCH.sub.2-[4-(trifluoro- A 1.480 621.0 methyl)pyrimidin-2-yl] 1-72 Cl, F, Cl NHCH.sub.2-(5-chloropyrimidin-2-yl) A 1.463 588.9 1-73 Cl, F, Cl NHCH.sub.2-(4-methyl-pyrimidin-2-yl) A 1.396 566.9 1-74 Cl, F, Cl NHCH.sub.2-(4,6-dimethyl- A 1.411 581.0 pyrimidin-2-yl) 1-75 Cl, F, Cl NHCH.sub.2-[4-methyl-6- A 1.496 635.0 (trifluoromethyl)pyrimidin-2-yl 1-76 Cl, F, H NHCH.sub.2-(2-pyrimidinyl) A 1.290 519.0 1-77 Cl, F, H NHCH.sub.2-(2-pyridyl) A 1.148 518.1 1-78 Cl, F, H NHCH.sub.2C(O)NHCH.sub.2CF.sub.3 A 1.300 566.0 1-79 Cl, F, H NH-(1,1-dioxo-thietan-3-yl) A 1.281 531.0 1-80 Cl, F, Cl H A 1.525 445.9 1-81 Cl, F, H OH A 1.346 428.0 1-82 Cl, F, Cl NHCH.sub.2-(2-methyl-tetrazol-5-yl) A 1.373 557.0 1-83 Cl, F, Cl NHCH.sub.2-(5-fluoro-pyrimidin-2-yl) A 1.418 571.0 1-84 Cl, F, Cl NH-(3-pyridyl) A 1.241 538.0 1-85 Cl, F, Cl NHNHC(O)NHCH.sub.2CF.sub.3 A 1.338 600.9 1-86 Cl, F, Cl NHCH.sub.2-(1,2,4-oxadiazol-3-yl) A 1.375 542.9 1-87 Cl, F, Cl NHCH.sub.2-(1,3,4-thiadiazol-2-yl) A 1.363 558.9 1-88 Cl, F, Cl NHCH.sub.2-(4-chloro-pyrimidin-2-yl) A 1.440 588.8 1-89 Cl, F, Cl NHCH.sub.2-(5-methyl-pyrimidin-2-yl) A 1.404 567.0 1-90 Cl, F, Cl NH-[(4R)-2-ethyl-3-oxo- A 1.393 574.1 isoxazolidin-4-yl] 1-91 Cl, F, Cl NHCH.sub.2CH.sub.2SO.sub.2CH.sub.3 A 1.336 567.0 1-92 Cl, F, Cl NHCH.sub.2-(1-methyl-1,2,3- A 1.332 556.0 triazol-4-yl) 1-93 Cl, F, Cl NHCH.sub.2-(1-methyl-1,2,4- A 1.307 556.0 triazol-3-yl) 1-94 Cl, F, Cl 3-ethyl-4-oxo-imidazolidin-1-yl A 1.375 558.0 1-95 Cl, F, Cl 4-oxo-3-(2,2,2- A 1.426 612.0 trifluoroethyl)imidazolidin-1-yl 1-96 Cl, F, Cl NHCH.sub.2-(1-methyl-tetrazol-5-yl) A 1.351 557.0 1-97 Cl, F, Cl NHNHC(O)NHCH.sub.2CF.sub.2H .sup.1H NMR (400 MHz, d.sub.6-DMSO): 10.0 (s, 1H), 8.2 (s, 1H), 7.8 (m, 2H), 7.6 (d, 1H), 7.5 (d, 1H), 6.8 (s, 1H), 6.2-5.8 (m, 1H), 4.5-4.3 (m, 2H), 3.6-3.4 (m, 2H), 3.2-3.0 (m, 4H), 2.1-1.9 (m, 2H) 1-98 Cl, F, Cl NHNHC(O)NHCH.sub.2CH.sub.3 A 1.309 547.0 1-99 Cl, F, Cl NH-(5-pyrimidinyl) A 1.404 539.0 1-100 Cl, F, Cl NHNHC(O)NHCH.sub.3 A 1.275 533.0 1-101 Cl, F, Cl NHCH.sub.2-(oxazol-2-yl) A 1.387 554.1 1-102 Cl, F, Cl NHN(CH.sub.3)-(2-pyrimidinyl) A 1.407 568.1 1-103 Cl, F, Cl NHCH.sub.2CH.sub.2SCH.sub.3 A 1.466 535.0 1-104 Cl, F, Cl NH-[2-oxo-1-(2,2,2- A 1.413 626.1 trifluoroethyl)pyrrolidin-3-yl] 1-105 Cl, F, Cl NH-(2-pyrazinyl) A 1.467 539.0 1-106 Cl, F, Cl NH-(1-methyl-pyrazol-3-yl) A 1.422 541.1 1-107 Cl, F, Cl NHCH.sub.2-(1- A 1.525 583.1 (trifluoromethyl)cyclopropyl) 1-108 Cl, F, Cl NH-(3-methyl-isothiazol-5-yl) A 1.460 558.0 1-109 Cl, F, Cl NHNH-(2-pyridyl) A 1.164 553.0 1-110 Cl, F, Cl NH-(3-pyridazinyl) A 1.419 539.0 1-111 Cl, F, Cl NHCH.sub.2-(1,3-dioxolan-2-yl) A 1.399 547.1 1-112 Cl, F, Cl NH-(1-methyl-2-oxo- A 1.336 558.0 pyrrolidin-3-yl) 1-113 Cl, F, Cl NHCH.sub.2-(4-pyrimidinyl) A 1.355 553.1 1-114 Cl, F, Cl NHCH.sub.2-(1-methyl-pyrazol-3-yl) A 1.376 555.1 1-115 Cl, F, Cl NHCH.sub.2CH.sub.2CF.sub.2H A 1.444 539.1 1-116 Cl, F, Cl NHCH.sub.2CH.sub.2-(1,3-dioxolan-2-yl) A 1.421 561.1 1-117 Cl, F, Cl NH-(1-ethyl-2-oxo-pyrrolidin-3-yl) A 1.369 572.1 1-118 Cl, F, Cl NHCH.sub.2-(4-oxazolyl) A 1.374 542.0 1-119 Cl, F, Cl NHCH.sub.2-(4-methyl-1,2,4- A 1.207 556.1 triazol-3-yl) 1-120 Cl, F, Cl NHCH.sub.2-(3-isoxazolyl) A 1.403 542.1 1-121 Cl, F, Cl NHCH.sub.2-(2-methyl-pyrazol-3-yl) A 1.369 555.1 1-122 Cl, F, Cl NH-(1-methyl-5-oxo-1,2,4- A 1.324 558.1 triazol-4-yl) 1-123 F, H, OCF.sub.3 NHCH.sub.2-(2-pyrimidinyl) A 1.342 569.1 1-124 F, H, OCF.sub.3 NHCH.sub.2-(2-pyridyl) A 1.177 568.1 1-125 Cl, F, Cl NH-[(4R)-2-methyl-3-oxo- A 1.358 560.1 isoxazolidin-4-yl] 1-126 Cl, F, Cl NHCH.sub.2-cyclopentyl A 1.558 543.0 1-127 Cl, F, Cl NHCH.sub.2-(2-tetrahydrofuranyl) A 1.439 545.1 1-128 Cl, F, Cl NHCH.sub.2CF.sub.2H A 1.438 524.9 1-129 Cl, F, Cl NHCH.sub.2CFH.sub.2 A 1.406 507.1 1-130 Cl, F, Cl NHCH.sub.2-(1-cyano- A 1.412 540.1 cyclopropyl) 1-131 Cl, F, Cl NH-(2,2-difluorocyclopropyl) A 1.450 537.0 1-132 Cl, F, Cl NHCH.sub.2-(1-oxo-thietan-3-yl) A 1.302 563.1 1-133 Cl, F, Cl NH-(4-pyridazinyl) A 1.277 539.0 1-134 F, H, OCF.sub.3 NH-(1,1-dioxo-thietan-3-yl) A 1.330 581.0 1-135 F, H, OCF.sub.3 NHCH.sub.2C(O)NHCH.sub.2CF.sub.3 A 1.356 616.1 1-136 Cl, F, Cl NS(CH.sub.2CH.sub.3).sub.2 A 1.349 549.0 1-137 Cl, F, Cl NH-(1-cyano-cyclobutyll) A 1.454 540.1 1-138 F, H, OCF.sub.3 NH-[(4R)-2-ethyl-3-oxo- A 1.363 590.1 isoxazolidin-4-yl]
Synthesis Example S.1
N-(Cyclopropylmethyl)-7-[5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]indane-4-carboxamide
(11) (Compound example 1-3; compound of formula C.1, wherein R.sup.2a and R.sup.2c are Cl, R.sup.2b is F, and Y is NHCH.sub.2-cyclopropyl)
(12) (7-Acetylindan-4-yl) trifluoromethanesulfonate (CAS 1312609-69-0) was synthesized as described in US 2011/0152246 (p. 118, compound I-IIIf).
Step 1: Methyl 7-acetylindane-4-carboxylate
(13) To a solution of (7-acetylindan-4-yl) trifluoromethanesulfonate (40 g) in methanol (357 mL) were added Na.sub.2CO.sub.3 (27.5 g) and [1,1-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) (Pd(dppf)Cl.sub.2, 9.5 g). The solution was pressurized with carbon monoxide (50 Psi) and heated at 50 C. for 5 h. Then, the mixture was filtered and the filtrate was concentrated. The residue was dissolved in CH.sub.2Cl.sub.2 and washed with brine, dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (18.3 g, 64%).
(14) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.9 (d, 1H), 7.7 (d, 1H), 4.0 (s, 3H), 3.3-3.2 (m, 4H), 2.6 (s, 3H), 2.1 (m, 2H).
Step 2: Methyl 7-[(3-(3,5-dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-but-2-enoyl]indane-4-carboxylate
(15) To a solution of the product of step 1 (12 g) and 1-(3,5-dichloro-4-fluoro-phenyl)-2,2,2-trifluoro-ethanone (28.7 g, CAS 1190865-44-1) in DCE (100 mL) was added K.sub.2CO.sub.3 (7.6 g) and triethylamine (7.6 mL). The reaction was stirred at reflux overnight. Then, the mixture was cooled to r.t., filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (18.75 g, 74%).
(16) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.8 (m, 1H), 7.5 (m, 1H), 7.3 (m, 1H), 7.2 (m, 2H), 3.9 (s, 3H), 3.2 (m, 2H), 3.1 (m, 2H), 2.0 (m, 2H).
Step 3: Methyl 7-[5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]indane-4-carboxylate (Compound Example 1-1)
(17) To a solution of the product of step 2 (10 g) in THF (167 mL) was added hydroxylamine hydrochloride (3 g), followed by a drop wise addition of a solution of NaOH (3.5 g) in water (83 mL). The reaction was stirred at r.t. overnight, and concentrated. The residue was taken up in ethyl acetate, and the organic layer was washed with water (3), dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (6 g, 58%).
(18) .sup.1H NMR (400 MHz, MeOH-d.sub.4): 7.9 (d, 1H), 7.8 (m, 2H), 7.4 (d, 1H), 4.3 (d, 1H), 4.1 (d, 1H), 3.9 (s, 3H), 3.3 (m, 2H), 3.2 (m, 2H), 2.1 (m, 2H).
Step 5: 7-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]indane-4-carboxylic acid (Compound Example 1-2)
(19) At 0 C., the product of step 4 (4.5 g) in THF (45 mL) was treated with a solution of LiOH (0.45 g) in water (5 mL), and the mixture stirred at r.t. for 5 h. Then, more LiOH (0.2 g) was added, and the reaction was stirred at r.t. overnight. Subsequently, 10% aqueous HCl was added to adjust the pH of the reaction to pH 3-4. The organic layer was diluted with CH.sub.2Cl.sub.2, washed with water (2), dried (Na.sub.2SO.sub.4), filtered, and concentrated. The obtained residue was purified by trituration (hexanes) to afford the product (3.35 g, 77%).
(20) .sup.1H NMR (400 MHz, d.sub.6-DMSO): 13.0 (s, 1H), 7.9-7.8 (m, 3H), 7.6-7.5 (m, 1H), 4.4-4.3 (m, 2H), 3.3-3.2 (m, 2H), 3.2-3.0 (m, 2H), 2.1-1.9 (m, 2H).
Step 6: N-(Cyclopropylmethyl)-7-[5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]indane-4-carboxamide (Compound Example 1-3)
(21) To a solution of the product of step 5 (0.23 g), cyclopropylmethylamine (0.04 g) and PyBroP (0.28 g) in CH.sub.2Cl.sub.2 (15 mL) at r.t. was added N,N-diisopropylethylamine (0.26 g). The reaction was stirred at r.t. overnight. Then, the reaction was diluted with CH.sub.2Cl.sub.2, washed with water (2), dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel to afford the product (0.21 g, 82%).
(22) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.6 (m, 2H), 7.5 (m, 1H), 7.2 (m, 1H), 6.0 (s, 1H), 4.2 (d, 1H), 3.8 (d, 1H), 3.4-3.3 (m, 2H), 3.3-3.1 (m, 4H), 2.2-2.1 (m, 2H), 1.1-1.0 (m, 1H), 0.6-0.5 (m, 2H), 0.3-0.2 (m, 2H).
C.2 Compound Examples 2
(23) Compound examples 2-1 to 2-24 correspond to compounds of formula C.2:
(24) ##STR00041##
wherein R.sup.2a, R.sup.2b, R.sup.2c and Y of each synthesized compound is defined in one row of table C.2 below.
(25) The compounds were synthesized in analogy to Synthesis Example S.2.
(26) TABLE-US-00003 TABLE C.2 HPLC-MS: Method, R.sub.t (min) & [M + H].sup.+ or Ex. R.sup.2a, R.sup.2b, R.sup.2c Y .sup.1H-NMR 2-1 Cl, F, Cl OH A 1.500 459.4 2-2 Cl, F, Cl OCH.sub.3 A 1.661 473.4 2-3 Cl, F, Cl NH-(1,1-dioxo-thietan-3-yl) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.5 (m, 2H), 7.35 (m, 2H), 7.2 (m, 1H), 6.7 (d, 1H), 5.0-4.85 (m, 2H), 4.7- 4.6 (m, 2H), 4.45 (d, 1H), 4.1-4.0 (m, 2H), 3.8 (d, 1H), 3.4 (d, 1H), 3.3-3.1 (m, 4H), 2.2-2.1 (m, 2H). 2-4 Cl, F, Cl NH-(thietan-3-yl) A 1.526 532.2 2-5 Cl, F, Cl NHCH.sub.2-(thietan-3-yl) A 1.527 544.8 2-6 Cl, F, Cl NHCH.sub.2-cyclopropyl A 1.393 514.6 2-7 Cl, F, Cl NHCH.sub.2C(O)NHCH.sub.2CF.sub.3 A 1.311 599.6 2-8 Cl, F, Cl NH-(1-oxo-thietan-3-yl) A 1.395 546.7 2-9 Cl, F, Cl NHCH.sub.2-(2-pyridyl) A 1.125 549.9 2-10 Cl, F, Cl NHCH.sub.2-(2-pyrimidinyl) A 1.284 550.9 2-11 Cl, F, Cl NHCH.sub.2-(1,1-dioxo-thietan- A 1.265 576.9 3-yl) 2-12 Cl, H, Cl NHNH-(2-pyrimidinyl) A 1.241 534.0 2-13 Cl, H, Cl NHCH.sub.2-(2-pyridyl) A 1.158 532.0 2-14 Cl, H, Cl NHCH.sub.2C(O)NHCH.sub.2CF.sub.3 A 1.302 580.0 2-15 Cl, H, Cl OH A 1.351 441.9 2-16 Cl, H, Cl OCH.sub.3 A 1.529 455.9 2-17 Cl, H, Cl NHCH.sub.2-(2-pyrimidinyl) A 1.291 533.0 2-18 Cl, H, Cl NH-cyclopropyl A 1.347 481.0 2-19 Cl, H, Cl NH-(1,1-dioxo-thietan-3-yl) A 1.289 545.0 2-20 Cl, H, Cl NHCH.sub.2-(4-thiazol) A 1.319 538.0 2-21 Cl, H, Cl NH-[(4R)-2-ethyl-3-oxo- A 1.325 554.0 isoxazolidin-4-yl] 2-22 Cl, H, Cl NHCH(CH.sub.3)- A 1.357 594.0 C(O)NHCH.sub.2CF.sub.3 2-23 Cl, H, Cl NH-(thietan-3-yl) A 1.404 513.0 2-24 Cl, H, Cl NH-(1-oxo-thietan-3-yl) A 1.232 529.0
Synthesis Example S.2
7-[3-(3,5-Dichloro-4-fluoro-phenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]-N-(1,1-dioxothietan-3-yl)indane-4-carboxamide
(27) (Compound example 2-3; compound of formula C.2, wherein R.sup.2a and R.sup.2c are Cl, R.sup.2b is F and Y is NH-(1,1,-dioxo-thietan-3-yl))
Step 1: Methyl 7-[3-(3,5-dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl]indane-4-carboxylate
(28) To a solution of methyl 7-[(3-(3,5-dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-but-2-enoyl]indane-4-carboxylate (i.e. the product of Synthesis Example S.1, step 2, 10 g) in CH.sub.3CN (400 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 16.6 g) and CH.sub.3NO.sub.2 (6 g) at r.t. The mixture was stirred for 20 min, and then adjusted to pH 6 with aqueous 1 M HCl solution. The aqueous phase was extracted with ethyl acetate (3150 mL). The organic layers were combined, concentrated and the obtained residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (6 g, 52%).
(29) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.89 (d, 1H), 7.66 (d, 1H), 7.21-7.19 (m, 2H), 5.52 (d, 1H), 5.39 (d, 1H), 4.04 (d, 1H), 3.91-3.87 (m, 4H), 3.25-3.15 (m, 2H), 3.06-2.99 (m, 2H), 2.1-1.9 (m, 2H).
Step 2: Methyl 7-[3-(3,5-dichloro-4-fluoro-phenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]indane-4-carboxylate (Compound 2-2)
(30) To a solution of the product of step 2 (6 g) in CH.sub.3OH (100 mL) was added acetic acid (100 mL) and iron powder (1.9 g). The mixture was stirred at 70 C. overnight, and then concentrated. Water (20 mL) was added and the aqueous layer was extracted with ethyl acetate (3100 mL). The combined organic layers were concentrated and the obtained residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (3.1 g, 56%).
(31) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.90 (d, 1H), 7.47 (d, 1H), 7.35-7.30 (m, 2H), 4.94 (d, 1H), 4.47 (d, 1H), 3.93 (s, 3H), 3.81 (d, 1H), 3.49 (d, 1H), 3.35-3.25 (m, 2H), 3.25-3.20 (m, 2H), 2.15-1.06 (m, 2H).
Step 3: 7-[3-(3,5-Dichloro-4-fluoro-phenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]indane-4-carboxylic acid (Compound 2-1)
(32) At 0 C., the product of step 2 (1.66 g) in THF (25 mL) was treated with a solution of LiOH (0.17 g) in water (10 mL), and the mixture stirred at r.t. overnight. Then, more LiOH (0.1 g) was added, and the reaction was stirred at 30 C. for 4 h. 10% aqueous HCl was added to adjust the pH of the reaction to pH 3-4. More water was added, and the aqueous layer was extracted with CH.sub.2Cl.sub.2 (3). The combined organic layers were dried (Na.sub.2SO.sub.4), filtered, and concentrated. The obtained residue was purified by trituration (hexanes) to afford the product (1.0 g, 62%).
(33) .sup.1H NMR (400 MHz, d.sub.6-DMSO): 13.0 (s, 1H), 7.9-7.75 (m, 3H), 7.75-7.6 (m, 1H), 4.9 (d, 1H), 4.45 (d, 1H), 3.9-3.7 (m, 2H), 3.3-3.1 (m, 2H), 2.1-1.9 (m, 2H).
Step 4: 7-[3-(3,5-Dichloro-4-fluoro-phenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]-N-(1,1-dioxothietan-3-yl)indane-4-carboxamide (Compound 2-3)
(34) To a solution of the product of step 3 (0.2 g), 1,1-dioxothietan-3-amine hydrochloride (0.08 g) and PyBroP (0.24 g) in CH.sub.2Cl.sub.2 (20 mL) at r.t. was added N,N-diisopropylethylamine (0.22 g). The reaction was stirred at r.t. overnight. Then, the reaction was diluted with CH.sub.2Cl.sub.2, washed with water (2), dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel to afford the product (0.15 g, 55%).
(35) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.5 (m, 2H), 7.35 (m, 2H), 7.2 (m, 1H), 6.7 (d, 1H), 5.0-4.85 (m, 2H), 4.7-4.6 (m, 2H), 4.45 (d, 1H), 4.1-4.0 (m, 2H), 3.8 (d, 1H), 3.4 (d, 1H), 3.3-3.1 (m, 4H), 2.2-2.1 (m, 2H).
C.3 Compound Examples 3
(36) Compound examples 3-1 to 3-13 correspond to compounds of formula C.3:
(37) ##STR00042##
wherein R.sup.2a, R.sup.2b, R.sup.2c and Y of each synthesized compound is defined in one row of table C.3 below.
(38) The compounds were synthesized in analogy to Synthesis Example S.3.
(39) TABLE-US-00004 TABLE C.3 HPLC-MS: Method, R.sub.t (min) & [M + H].sup.+ or Ex. R.sup.2a, R.sup.2b, R.sup.2c Y .sup.1H-NMR (400 MHz, CDCl.sub.3) 3-1 Cl, H, Cl OCH.sub.3 7.64 (d, 1H), 7.51 (s, 2H), 7.45 (s, 1H), 7.18 (d, 1H), 4.09 (d, 2H), 3.90 (s, 3H), 3.73 (d, 1H), 3.08 (m, 2H), 2.94 (m, 2H), 1.86-1.72 (m, 4H) 3-2 Cl, H, Cl OH .sup.1H NMR (400 MHz, CDCl.sub.3): 7.87 (d, 1H), 7.65 (s, 2H), 7.50 (s, 1H), 7.23 (d, 1H), 4.11 (d, 1H), 3.74 (d, 1H), 3.19 (m, 2H), 2.97 (m, 2H), 1.82-1.81 (m, 4H). 3-3 Cl, H, Cl NH-(1,1-dioxo-thietan-3-yl) A 1.361 561.0 3-4 Cl, H, Cl NHCH.sub.2C(O)NHCH.sub.2CF.sub.3 A 1.391 596.0 3-5 Cl, H, Cl NHCH.sub.2CF.sub.3 A 1.466 539.0 3-6 Cl, H, Cl NH-cyclopropyl A 1.424 497.0 3-7 Cl, H, Cl NH-(thietan-3-yl) A 1.446 529.0 3-8 Cl, H, Cl NHCH(CH.sub.3)- A 1.400 610.0 C(O)NHCH.sub.2CF.sub.3 3-9 Cl, H, Cl NH-[(4R)-2-ethyl-3-oxo- A 1.379 570.0 isoxazolidin-4-yl] 3-10 Cl, H, Cl NHCH.sub.2-(thiazol-4-yl) A 1.389 554.0 3-11 Cl, H, Cl NHCH.sub.2-(2-pyrimidinyl) A 1.371 549.0 3-12 Cl, H, Cl NHCH.sub.2-(2-pyridyl) A 1.243 548.0 3-13 Cl, H, Cl NH-(1-oxo-thietan-3-yl) A 1.293 545.0
Synthesis Example S.3
8-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(2,2,2-trifluoroethyl)tetralin-5-carboxamide
(40) (Compound example 3-5; compound of formula C.3, wherein R.sup.2a and R.sup.2c are Cl, R.sup.2b is H, and Y is NHCH.sub.2CF.sub.3)
Step 1: 5-Methoxytetralin
(41) To a mixture of tetralin-5-ol (32 g) and K.sub.2CO.sub.3 (64 g) in acetone (600 mL) was added (CH.sub.3).sub.2SO.sub.4 (60 g), and the mixture was stirred at reflux for 15 h. Then, the mixture was filtered and concentrated. The crude product was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (34 g, 88%).
(42) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.12 (m, 1H), 6.81-6.70 (m, 2H), 3.86 (s, 3H), 2.81 (m, 2H), 2.71 (m, 2H), 1.91-1.77 (m, 4H).
Step 2: 1-(8-Methoxytetralin-5-yl)ethanone
(43) At 0 C., acetyl chloride (AcCl, 16 g) was added dropwise to a mixture of the product of step 1 (25 g) and AlCl.sub.3 (28 g) in DCE (300 mL). The reaction was stirred at 25 C. for 10 h, and then poured into ice water (200 mL). The aqueous layer was extracted with CH.sub.2Cl.sub.2 (3300 mL), and the combined organic layers were dried (Na.sub.2SO.sub.4), filtered and concentrated to give the crude product (27 g) which was used in the next step without any further purification.
(44) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.64 (d, 1H), 6.71 (d, 1H), 3.89 (s, 3H), 3.10-3.00 (m, 2H), 2.68 (m, 2H), 2.56 (s, 3H), 1.83-1.68 (m, 4H).
Step 3: 1-(8-Hydroxytetralin-5-yl)ethanone
(45) The crude product of step 2 (30 g) in DCE (1.5 L) was treated with AlCl.sub.3 (30 g) and the mixture was stirred at 100 C. overnight. Then, the solution was poured into ice water (500 mL) and extracted with CH.sub.2Cl.sub.2. The combined organic layers were dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (15 g, 50%).
(46) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.56 (d, 1H), 6.69 (d, 1H), 3.06 (m, 2H), 2.68 (m, 2H), 2.56 (s, 3H), 1.87-1.80 (m, 2H), 1.80-1.72 (m, 2H).
Step 4: (8-Acetyltetralin-5-yl) trifluoromethanesulfonate
(47) To the product of step 3 (15 g) and Et.sub.3N (20 g) in CH.sub.2Cl.sub.2 (500 mL) at 0 C. was added triflic anhydride (Tf.sub.2O, 33 g). The mixture was stirred at 0 C. for 30 min. Then, the solution was poured onto ice water (500 mL) and extracted with CH.sub.2Cl.sub.2. The combined organic layers were dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (25 g, 95%).
(48) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.55-7.46 (m, 1H), 7.18 (m, 1H), 3.03-2.95 (m, 2H), 2.84 (m, 2H), 2.58 (s, 3H), 1.91-1.79 (m, 4H).
Step 5: Methyl 8-acetyltetralin-5-carboxylate
(49) To a solution of the product of step 4 (25 g) in methanol (500 mL) were added Na.sub.2CO.sub.3 (30 g) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)C.sub.12, 3 g). The solution was pressurized with carbon monoxide (50 Psi) and heated at 50 C. overnight. Then, the mixture was filtered and the filtrate was concentrated. The residue was dissolved in CH.sub.2Cl.sub.2 and washed with water, dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (15 g, 65%).
(50) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.63 (d, 1H), 7.34 (d, 1H), 3.89 (s, 3H), 3.04 (m, 2H), 2.92 (m, 2H), 2.57 (s, 3H), 1.77 (m, 4H).
Step 6: Methyl 8-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-but-2-enoyl]tetralin-5-carboxylate
(51) To a solution of the product of step 5 (10 g) and 1-(3,5-dichlorophenyl)-2,2,2-trifluoro-ethanone (15.7 g, CAS 130336-16-2) in DCE (100 mL) was added K.sub.2CO.sub.3 (5.9 g) and Et.sub.3N (10 mL). The reaction was stirred for 16 h at 100 C. Then, the mixture was filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (17 g, 86%).
(52) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.66 (d, 1H), 7.38 (s, 2H), 7.34 (d, 1H), 7.11 (m, 2H), 4.01 (s, 3H), 3.11-3.03 (m, 2H), 2.88 (m, 2H), 1.87-1.77 (m, 4H).
Step 7: Methyl 8-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]tetralin-5-carboxylate (Compound Examples 3-1)
(53) To a solution of the product of step 2 (17 g) in DCE (500 mL) was added hydroxylamine hydrochloride (5.3 g) and tetrabutylammoniumbromid (TBAB, 6.2 g), followed by drop wise addition of a solution of NaOH (6.1 g) in water (70 mL). The reaction was stirred for 12 h at 25 C. The organic layer was washed with water (3100 mL), dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford the product (12 g, 67%).
(54) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.64 (d, 1H), 7.51 (s, 2H), 7.45 (s, 1H), 7.18 (d, 1H), 4.09 (d, 2H), 3.90 (s, 3H), 3.73 (d, 1H), 3.08 (m, 2H), 2.94 (m, 2H), 1.86-1.72 (m, 4H).
Step 8: 8-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]tetralin-5-carboxylic acid (Compound Examples 3-2)
(55) The product of step 7 (12 g) in THF (100 mL) was treated with a solution of LiOH (3 g) in water (30 mL), and the mixture stirred at r.t. for 12 h and at 80 C. for 5 h. Then, the pH of the reaction adjusted to pH 3 using 1 M aqueous HCl solution. The aqueous layer was extracted with methyl-tert-butylether (MTBE, 3100 mL). The organic layers were combined, dried (Na.sub.2SO.sub.4), filtered, and concentrated to afford the product (10 g, 88%).
(56) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.87 (d, 1H), 7.65 (s, 2H), 7.50 (s, 1H), 7.23 (d, 1H), 4.11 (d, 1H), 3.74 (d, 1H), 3.19 (m, 2H), 2.97 (m, 2H), 1.82-1.81 (m, 4H).
Step 9: 8-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(2,2,2-trifluoroethyl)tetralin-5-carboxamide
(57) To a solution of the product of step 8 (0.3 g), 2,2,2-trifluoroethylamine (0.08 g) and PyBroP (0.37 g) in CH.sub.2Cl.sub.2 (10 mL) at r.t. was added N,N-diisopropylethylamine (0.27 g). The reaction was stirred at r.t. overnight. Then, the reaction was concentrated to give a residue, which was purified by flash chromatography on silica gel to afford the product (0.19 g, 52%).
(58) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.55 (s, 2H), 7.45 (s, 1H), 7.2 (d, 1H), 7.1 (d, 1H), 6.0 (m, 1H), 4.2-4.0 (m, 3H), 3.7 (d, 1H), 2.9 (m, 2H), 2.85 (m, 2H), 1.8-1.7 (m, 4H).
C.4 Compound Examples 4
(59) Compound examples 4-1 to 4-2 correspond to compounds of formula C.4:
(60) ##STR00043##
wherein R.sup.111, R.sup.222 and Y of each compound is defined in one row of table C.4 below.
(61) The compounds 4-1 and 4-2 were obtained from the corresponding racemic compound example 1-7 by separation using a preparative chiral HPLC (method B). Assignment of the absolute configuration was done by X-ray crystallography.
(62) Method B (preparative chiral HPLC). Instrument: Thar SFC Pre-80. Column: Chiralpak AS-H 5 mm, 3.0 cm id25 cm L Mobile phase: A for SFC CO.sub.2 and B for MeOH (0.1% NH.sub.4OH). Gradient: A:B=65:35. Flow rate: 70 mL/min. Detection wavelength: 220 nm. System Back Pressure: 100 bar.
(63) Method C (analytical chiral HPLC). Instrument: Thar analytical SFC. Column: Chiralpak AS-H 5 mm, 0.46 cm id15 cm L Mobile phase: A for SFC CO.sub.2 and B for Methanol (0.05% Isopropylamine). Gradient: B in A from 10% to 40% in 5 minutes. Flow rate: 4.0 mL/min. Detection wavelength: 220 nm. System Back Pressure: 100 bar.
(64) TABLE-US-00005 TABLE C.4 Chiral analytical HPLC Method, Ex. R.sup.111 R.sup.222 Y retention time 4-1 3,5-Dichloro-4- CF.sub.3 NHCH.sub.2-(2- C 2.78 min fluoro-phenyl pyrimidinyl) 4-2 CF.sub.3 3,5-Dichloro-4- NHCH.sub.2-(2- C 3.44 min fluoro-phenyl pyrimidinyl)
C.5 Compound Examples 5
(65) Compound examples 5-1 to 5-2 corresponds to compounds of formula C.5:
(66) ##STR00044##
wherein R.sup.2a, R.sup.2b, R.sup.2c R.sup.3a, R.sup.3b and Y of each synthesized compound is defined in one row of table C.5 below.
(67) The compounds were synthesized in analogy to Synthesis Example S.4.
(68) TABLE-US-00006 TABLE C.5 HPLC-MS: Method, R.sub.t (min) & [M + H].sup.+ or Ex. R.sup.2a, R.sup.2b, R.sup.2c R.sup.3a, R.sup.3b Y .sup.1H-NMR 5-1 Cl, F, Cl F, H OCH.sub.3 .sup.1H NMR (400 MHz, CDCl.sub.3): 7.9 (d, 1H), 7.6 (m, 2H), 7.45 (d, 1H), 6.5 (d, 1H), 3.9 (s, 3H), 3.35 (m, 2H), 3.2 (m, 2H), 2.15 (m, 2H) 5-2 Cl, F, Cl F, H NHCH.sub.2-(2-pyridyl) A 1.248 570.0
Synthesis Example S.4
7-[5-(3,5-Dichloro-4-fluoro-phenyl)-4-fluoro-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(2-pyridylmethyl)indane-4-carboxamide
(69) (Compound example 5-2; compound of formula C.5, wherein R.sup.2a and R.sup.2c are Cl, R.sup.2b is F, R.sup.3a is F and R.sup.3b is H, and Y is NHCH.sub.2-(2-pyridyl))
Step 1: Methyl 7-[5-(3,5-dichloro-4-fluoro-phenyl)-4-fluoro-5-(trifluoromethyl)-4H-isoxazol-3-yl]indane-4-carboxylate (Compound Example 5-1)
(70) To a solution of 7-[5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]indane-4-carboxylate (compound example 1-1, 2 g) in THF (30 mL) under nitrogen at 78 C. was added), lithium hexamethyldisilazide (LiHMDS, 4.6 mL, 1 M solution in THF) and the mixture was stirred for 1.5 h at 78 C. Then, N-fluorobenzenesulfonimide (NFSI, 1.7 g) was added at 78 C. in one portion and the mixture was stirred at 78 C. for another 3 h. Then, the reaction was quenched with saturated aqueous NH.sub.4Cl solution. Ethyl acetate was added (300 mL) and the organic layer was washed with water (3), dried (Na.sub.2SO.sub.4), filtered, and concentrated to afford a residue that was purified by flash chromatography on silica gel (ethyl acetate/cyclohexane) to afford the product (0.4 g, 19%).
(71) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.9 (d, 1H), 7.6 (m, 2H), 7.45 (d, 1H), 6.5 (d, 1H), 3.9 (s, 3H), 3.35 (m, 2H), 3.2 (m, 2H), 2.15 (m, 2H).
Step 2: 7-[5-(3,5-Dichloro-4-fluoro-phenyl)-4-fluoro-5-(trifluoromethyl)-4H-isoxazol-3-yl]indane-4-carboxylic acid
(72) The product of step 1 (0.4 g) in THF (7.5 mL) was treated with a solution of LiOH (0.08 g) in water (2.5 mL), and the mixture stirred at r.t. overnight. Then, diethyl ether (300 mL) was added and the pH of the solution was adjusted to pH 3-4 using 10% aqueous HCl solution. The organic layer was separated, washed with water (2), dried (Na.sub.2SO.sub.4), filtered, and concentrated to afford the product (0.37 g, 95%), which was used in the next step without any further purification.
Step 3: 7-[5-(3,5-Dichloro-4-fluoro-phenyl)-4-fluoro-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(2-pyridylmethyl)indane-4-carboxamide (Compound Example 5-2)
(73) To a solution of the product of step 2 (0.36 g), 2-picolylamine (0.1 g, CAS 3731-51-9) and PyBroP (0.42 g) in CH.sub.2Cl.sub.2 (40 mL) at r.t. was added N,N-diisopropylethylamine (0.31 g). The reaction was stirred at r.t. overnight. Then, the reaction was quenched with water. The organic layer was separated, dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel to afford the product (0.29 g, 68%).
(74) HPLC-MS (method A): 1.248 min, M=570.0.
C.6 Compound Examples 6
(75) Compound example 6-1 corresponds to a compound of formula C.6:
(76) ##STR00045##
wherein R.sup.2a, R.sup.2b, R.sup.2c and Y of each synthesized compound is defined in one row of table C.6 below.
(77) The compound was synthesized in analogy to Synthesis Example S.5.
(78) TABLE-US-00007 TABLE C.6 HPLC-MS: Method, R.sub.t (min) & Ex. R.sup.2a, R.sup.2b, R.sup.2c Y [M + H].sup.+ or .sup.1H-NMR 6-1 Cl, H, Cl NHCH.sub.2-(2-pyridyl) A 1.248 570.0
Synthesis Example S.5
7-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(2-pyridylmethyl)indane-4-carbothioamide
(79) (Compound example 6-1; compound of formula C.5, wherein R.sup.2a and R.sup.2c are Cl, R.sup.2b is H, and Y is NHCH.sub.2-(2-pyridyl))
(80) A solution of 7-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(2-pyridylmethyl)indane-4-carboxamide (compound example 1-27, 190 mg) and Lawesson's reagent (90 mg, CAS 19172-47-5) in toluene (15 mL) was refluxed for 5 h and then stirred at r.t. overnight. Ethyl acetate was added (200 mL) and the organic layer was washed with water (3), dried (Na.sub.2SO.sub.4), filtered and concentrated to give a residue, which was purified by flash chromatography on silica gel to afford the product (70 mg, 60%).
(81) HPLC-MS (method A): 1.335 min, M=550.0.
II. Evaluation of Pesticidal Activity
(82) The activity of the compounds of formula I of the present invention can be demonstrated and evaluated by the following biological test.
(83) B.1 Diamond back moth (Plutella xylostella)
(84) The active compound was dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water: acetone. Surfactant (Kinetic HV) was added at a rate of 0.01% (vol/vol). The test solution was prepared at the day of use.
(85) Leaves of cabbage were dipped in test solution and air-dried. Treated leaves were placed in petri dishes lined with moist filter paper and inoculated with ten 3.sup.rd instar larvae. Mortality was recorded 72 hours after treatment.
(86) In this test, the compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-69, 1-70, 1-71, 1-72, 2-1, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-3, 3-4, 3-5, 3-6, 4-1, 4-2 at 300 ppm, respectively, showed a mortality of at least 75% in comparison with untreated controls.
(87) B.2 Green Peach Aphid (Myzus persicae)
(88) For evaluating control of green peach aphid (Myzus persicae) through systemic means the test unit consisted of 96-well-microtiter plates containing liquid artificial diet under an artificial membrane.
(89) The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were pipetted into the aphid diet, using a custom built pipetter, at two replications.
(90) After application, 5-8 adult aphids were placed on the artificial membrane inside the microtiter plate wells. The aphids were then allowed to suck on the treated aphid diet and incubated at about 231 C. and about 505% relative humidity for 3 days. Aphid mortality and fecundity was then visually assessed.
(91) In this test, the compounds 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-69, 1-70, 1-71, 1-72, 1-73, 1-74, 1-75, 1-76, 1-77, 1-78, 1-79, 1-80, 1-82, 2-1, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-3, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-10, 3-11, 3-12, 3-13, 4-1, 4-2 at 2500 ppm, respectively, showed a mortality of at least 75% in comparison with untreated controls.
(92) B.3 Vetch Aphid (Megoura viciae)
(93) For evaluating control of vetch aphid (Megoura viciae) through contact or systemic means the test unit consisted of 24-well-microtiter plates containing broad bean leaf disks.
(94) The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the leaf disks at 2.5 l, using a custom built micro atomizer, at two replications.
(95) After application, the leaf disks were air-dried and 5-8 adult aphids placed on the leaf disks inside the microtiter plate wells. The aphids were then allowed to suck on the treated leaf disks and incubated at about 231 C. and about 505% relative humidity for 5 days. Aphid mortality and fecundity was then visually assessed.
(96) In this test, the compounds 1-1, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-69, 1-70, 1-71, 1-72, 1-73, 1-74, 1-75, 1-76, 1-77, 1-78, 1-79, 1-80, 1-82, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-3, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-10, 3-11, 3-12, 3-13, 4-1, 4-2 at 2500 ppm, respectively, showed a mortality of at least 75% in comparison with untreated controls.
(97) B.4 Tobacco Budworm (Heliothis virescens)
(98) For evaluating control of tobacco budworm (Heliothis virescens) the test unit consisted of 96-well-microtiter plates containing an insect diet and 15-25 H. virescens eggs.
(99) The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 10 l, using a custom built micro atomizer, at two replications.
(100) After application, microtiter plates were incubated at about 281 C. and about 805% relative humidity for 5 days. Egg and larval mortality was then visually assessed.
(101) In this test, the compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-68, 1-69, 1-70, 1-71, 1-72, 1-73, 1-74, 1-75, 1-76, 1-77, 1-78, 1-79, 1-80, 1-82, 2-1, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-3, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-10, 3-11, 3-12, 3-13, 4-1, 4-2 at 2500 ppm, respectively, showed a mortality of at least 75% in comparison with untreated controls.
(102) B.5 Boll Weevil (Anthonomus grandis)
(103) For evaluating control of boll weevil (Anthonomus grandis) the test unit consisted of 96-well-microtiter plates containing an insect diet and 5-10 A. grandis eggs.
(104) The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 5 l, using a custom built micro atomizer, at two replications.
(105) After application, microtiter plates were incubated at about 251 C. and about 755% relative humidity for 5 days. Egg and larval mortality was then visually assessed.
(106) In this test, the compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-69, 1-70, 1-71, 1-72, 1-73, 1-74, 1-75, 1-76, 1-77, 1-78, 1-79, 1-80, 1-81, 1-82, 2-1, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-16, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-2, 3-3, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-10, 3-11, 3-12, 3-13, 4-1, 4-2 at 2500 ppm, respectively, showed a mortality of at least 75% in comparison with untreated controls.
(107) B.6 Mediterranean Fruitfly (Ceratitis capitata)
(108) For evaluating control of Mediterranean fruitfly (Ceratitis capitata) the test unit consisted of microtiter plates containing an insect diet and 50-80 C. capitata eggs.
(109) The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 5 l, using a custom built micro atomizer, at two replications.
(110) After application, microtiter plates were incubated at about 281 C. and about 805% relative humidity for 5 days. Egg and larval mortality was then visually assessed.
(111) In this test, the compounds 1-1, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-69, 1-70, 1-71, 1-72, 1-73, 1-74, 1-75, 1-76, 1-77, 1-78, 1-79, 1-80, 1-82, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-16, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-3, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-10, 3-11, 3-12, 3-13, 4-1, 4-2 at 2500 ppm showed a mortality of at least 75% in comparison with untreated controls.
(112) B.7 Orchid Thrips (Dichromothrips corbetti)
(113) Dichromothrips corbetti adults used for bioassay were obtained from a colony maintained continuously under laboratory conditions. For testing purposes, the test compound is diluted in a 1:1 mixture of acetone:water (vol:vol), plus Kinetic HV at a rate of 0.01% v/v.
(114) Thrips potency of each compound was evaluated by using a floral-immersion technique. All petals of individual, intact orchid flowers were dipped into treatment solution and allowed to dry in Petri dishes. Treated petals were placed into individual re-sealable plastic along with about 20 adult thrips. All test arenas were held under continuous light and a temperature of about 28 C. for duration of the assay. After 3 days, the numbers of live thrips were counted on each petal. The percent mortality was recorded 72 hours after treatment.
(115) In this test, the compounds 1-1, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-68, 1-69, 1-70, 1-71, 1-72, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-3, 3-4, 3-5, 3-6, 4-1, 4-2 at 300 ppm, respectively, showed a mortality of at least 75% in comparison with untreated controls.
(116) B.8 Rice Green Leafhopper (Nephotettix virescens)
(117) Rice seedlings were cleaned and washed 24 hours before spraying. The active compounds were formulated in 1:1 acetone:water (vol:vol), and 0.01% vol/vol surfactant (Kinetic HV) was added. Potted rice seedlings were sprayed with 5-6 ml test solution, air dried, covered with Mylar cages and inoculated with 10 adults.
(118) Treated rice plants were kept at about 28-29 C. and relative humidity of about 50-60%. Percent mortality was recorded after 72 hours.
(119) In this test, the compounds 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-69, 1-70, 1-71, 1-72, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-17, 2-18, 2-19, 2-20, 2-21, 2-23, 2-24, 3-3, 3-4, 3-5, 3-6, 4-2 at 300 ppm, respectively, showed a mortality of at least 75% in comparison with untreated controls.
(120) B.9 Red Spider Mite (Tetranychus kanzawai)
(121) The active compound was dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water: acetone. Add surfactant (Kinetic HV) was added at a rate of 0.01% (vol/vol). The test solution was prepared at the day of use.
(122) Potted cowpea beans of 4-5 days of age were cleaned with tap water and sprayed with 1-2 ml of the test solution using air driven hand atomizer. The treated plants were allowed to air dry and afterwards inoculated with 30 or more mites by clipping a cassava leaf section from rearing population. Treated plants were placed inside a holding room at about 25-27 C. and about 50-60% relative humidity. Percent mortality was assessed 72 hours after treatment.
(123) In this test, the compounds 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-18, 1-20, 1-21, 1-22, 1-23, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-69, 1-70, 1-71, 1-72, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-3, 3-4, 3-5, 3-6, 4-2 at 300 ppm showed a mortality of at least 75% in comparison with untreated controls.
(124) B.10 Southern Armyworm (Spodoptera eridania)
(125) The active compounds were formulated in cyclohexanone as a 10,000 ppm solution supplied in tubes. The tubes were inserted into an automated electrostatic sprayer equipped with an atomizing nozzle and they served as stock solutions for which lower dilutions were made in 50% acetone:50% water (v/v). A nonionic surfactant (Kinetic) was included in the solution at a volume of 0.01% (v/v).
(126) Lima bean plants (variety Sieva) were grown 2 plants to a pot and selected for treatment at the 1.sup.st true leaf stage. Test solutions were sprayed onto the foliage by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood and then removed from the sprayer. Each pot was placed into perforated plastic bags with a zip closure. About 10 to 11 armyworm larvae were placed into the bag and the bags zipped closed. Test plants were maintained in a growth room at about 25 C. and about 20-40% relative humidity for 4 days, avoiding direct exposure to fluorescent light (24 hour photoperiod) to prevent trapping of heat inside the bags. Mortality and reduced feeding were assessed 4 days after treatment, compared to untreated control plants.
(127) In this test, the compounds 1-5, 1-6, 1-7, 1-10, 1-12, 1-14, 1-16, 1-17, 1-21, 1-23, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-38, 1-42, 1-49, 1-51, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 4-2 at 1 ppm showed a mortality of at least 75% in comparison with untreated controls.
(128) B.11 Green Soldier Stink Bug (Nezara viridula)
(129) The active compound was dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water: acetone. Surfactant (Kinetic HV) was added at a rate of 0.01% (vol/vol). The test solution was prepared at the day of use.
(130) Soybean pods were placed in glass Petri dishes lined with moist filter paper and inoculated with ten late 3rd instar N. viridula. Using a hand atomizer, approximately 2 ml solution is sprayed into each Petri dish. Assay arenas were kept at about 25 C. Percent mortality was recorded after 5 days.
(131) In this test, the compounds 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-20, 1-21, 1-22, 1-23, 1-25, 1-26, 1-27, 1-28, 1-29, 1-3, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-38, 1-39, 1-40, 1-41, 1-42, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-53, 1-54, 1-55, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-72, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11, 2-12, 2-13, 2-14, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 2-24, 3-3, 3-4, 4-2 at 300 ppm showed a mortality of at least 75% in comparison with untreated controls.
(132) B.12 Neotropical Brown Stink Bug (Euschistus heros)
(133) The active compound was dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water: acetone. Surfactant (Kinetic HV) was added at a rate of 0.01% (vol/vol). The test solution was prepared at the day of use.
(134) Soybean pods were placed in microwavable plastic cups and inoculated with ten adult stage E. heros. Using a hand atomizer, approximately 1 ml solution is sprayed into each cup, insects and food present. A water source was provided (cotton wick with water). Each treatment was replicated 2-fold. Assay arenas were kept at about 25 C. Percent mortality was recorded after 5 days.
(135) In this test, the compounds 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-17, 1-18, 1-20, 1-21, 1-23, 1-25, 1-26, 1-27, 1-28, 1-30, 1-31, 1-32, 1-33, 2-3, 2-4, 2-6, 2-7, 2-8, 2-9, 2-10, 2-11 at 100 ppm showed a mortality of at least 75% in comparison with untreated controls.
(136) B.13 Brown Marmorated Stink Bug (Halyomorpha halys)
(137) The active compound was dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water: acetone. Surfactant (Kinetic HV) was added at a rate of 0.01% (vol/vol). The test solution was prepared at the day of use.
(138) Row peanuts and soybean seeds were placed into microwavable plastic cups and inoculated with five adult stage H. halys. Using a hand atomizer, approximately 1 ml solution is sprayed into each cup, insects and food present. A water source was provided (cotton wick with water). Each treatment is replicated 4-fold. Assay arenas are kept at about 25 C. Percent mortality was recorded after 5 days.
(139) In this test, the compounds 1-3, 1-4, 1-5, 1-6, 1-7, 1-9, 1-11, 1-12, 1-14, 1-16, 1-20, 1-21, 1-25, 1-26, 1-27, 1-28, 1-30, 1-31, 1-32, 1-33, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10 at 100 ppm showed a mortality of at least 75% in comparison with untreated controls.